1. A New Medical Option for Termination of Pregnancy: Introducing Mifegymiso
CLEVE ZIEGLER, M.D. FRCS
JEWISH GENERAL HOSPITAL
Mcgill annual update in family medicine 2018

2. Conflicts of Interest:
Advisory Board: Allergan, Abbvie, Bayer
Speaker: Allergan, Abbvie , Bayer

3. Objectives:
1. Review the use of Mifepristone and Misoprostol for medical abortion
2. Overview of the present landscape in Quebec
3. Review the guidelines and recommendation of the College Des Medecins du Quebec

4. What is Medical Abortion?
Termination of early intrauterine pregnancy < 8 weeks from LMP with medication rather than surgical evacuation
Combination of Mifepristone and Misoprostol (M&M) has been used widely in China and France (1988) , Sweden and Great Britain (1992), and USA (2000) 2015 for pregnancy < 49 days from LMP
2015: Approved in Canada for pregnancy < 49 days
2017: Approved in Canada for pregnancy < 63 days
2017 ( December): Available in Quebec

5. Canadian Landscape: 100,000 abortions/ year in Canada 25,000 Quebec
50% pregnancies unplanned
50% unplanned pregnancies are terminated
40% in women using contraception

6. Features of Medical vs. Surgical Abortion
Effective (>95%) < 63 days
Acceptable ( 63-96%)
Avoid surgery
Very early intervention
May take days
Significant cramps and bleeding
Discrete and private
Several visits for follow up
D&C 1.6%
FREE IN QUEBEC
Highly effective (>99%)
Very acceptable ( %)
Allows for sedation and analgesia
6 weeks +
Takes minutes
Negligible
Clinic or hospital
Few visits
D&C 1%
FREE IN QUEBEC

7. Comparison of Morbidity: Medical Vs. Surgical Abortion

8. Key Data: Medical vs. Surgical
No need for subsequent Intervention: 95-98%
Surgical Aspiration: 1.6%
Ongoing Pregnancy: %
Infection: 0.18%
Limits: < 63 days from LMP
Cost: None
99% 1%
<< 1%
0.5%
20 weeks
None

9. Mifegymiso

10. Mifegymiso: Mifepristone 200 mg+ Misoprostil 800 mcg

11. Mifegymiso: Mifepristone and Misoprostol
Mifepristone (RU-486) 200mg
Misoprostol 800 mcg

12. Mifepristone 200 mg dose Rapid absorption
Peak serum levels 1-2 hours after administration
Metabolized by CYP P 450
Fecal excretion

13. SPRMs: Agonistic vs. Antagonistic Effects
Onapristone
Mifepristone
Ulipristal acetate
Asoprisnil
Telapristone acetate
J 1042
Progesterone
R5020 (synthetic
progestin)
Mesoprogestins
Agonists
Antagonists

14. Basal transcription apparatus
SPRMs Act as Progesterone Agonists or Antagonists Depending on the Target Tissue
SPRMs
Basal transcription apparatus
Transcription activation (progesterone agonism)
No transcription activation (progesterone antagonism) PR
Co-activators
Co-repressors
Progesterone response element
Chabbert-Buffet N, et al. Hum Reprod Update 2005;11: Madauss KP, et al. Mol Endocrinol 2007;21: Spitz IM. Curr Opin Investig Drugs 2006;7:882-90 14 14

15. Misoprostol

16. Mechanism of Action: M&M

17. Misoprostol: Pharmacokinetics

18. Protocol for Administration:
Oral administration of Mifepristone 200 mg (single pill) followed by administration of 800 mcg Misoprostol hours later
Misoprostol: Buccal administration 4 pills , maintain between cheek and gums for 30 minutes, swallow remaining fragments with water
Analgesics
RH immune globulin prn
IMPORTANT TO ENSURE FOLLOW UP 7-14 DAYS LATER TO ENSURE COMPLETED PREGNANCY TERMINATION

19. Side effects: Frequent ( 10%) Rare ( 1%)
GI :( nausea, diarrhea, vomiting , abdominal pain
NRO: Headache
GYN: cramps, bleeding
GEN: fever, chills, dizziness, fatigue
GI: cramping
GYN: prolonged bleeding, mastalgia
ID: Endometritis

22. CMQ Guidelines for Use

23. CMQ Guidelines: Ultrasound

24. CMQ Guidelines: Follow up

25. CMQ Guidelines for Follow Up
US for confirmation of evacuation of pregnancy
Serum hcg: Reduction of > 80% is associated with complete abortion
< 80% requires US for confirmation

27. Role of Antibiotic Prophylaxis?
Used fairly systematically in surgical TOP with reduction on infectious morbidity
Doxycycline 200 mg p.o. single dose
No date for medical TOP
NNT: 2,500

29. Primary Outcome: Gestational Sac Expulsion by First Follow up Visit

30. Initiation of Contraception
Rapid return of ovulation /- 5.1 days
As early as 8 days post abortion
Can initiate hormonal contraception same or following day as administration of Misoprostol
Barrier methods can be used immediately
IUD/IUS insertion with conformation of successful TOP

31. Conclusions:
Combination of Mifepristone and Misoprostol provide an effective option for early medical abortion
Evaluate for contraindications prior to use
Patient counselling is essential
Accurate determination of gestational age is essential, preferable by ultrasound
Follow up must be assured to confirm successful termination of pregnancy